Rheumatoid factor was tested for complement-dependent cytotoxicity to malignant melanoma cells. When incubated for 90 minutes in the presence of normal human plasma, 20-53% of the melanoma cells were injured. Two substances, one in the rheumatoid plasma and the second in the normal plasma, contributed to the cytotoxic effect. The substance in rheumatoid plasma was present in high titer. The role of complement in this cytotoxicity system was established by measuring C1q binding by melanoma cells. C1q binding was increased when tumor cells were incubated with both plasma plasmas but not when incubated with normal or rheumatoid plasma alone. The sequence by which normal and rheumatoid plasmas are added to the incubations is also important; toxicity is not recorded when rheumatoid plasma is added before the other incubation components. The low titer substance in normal plasma is present in 70% of specimens, is not present in Ig deficient or cord blood plasma and may be an acquired antibody. It is also absent from plasmas that contain rheumatoid factor. The components that contributed to rheumatoid factor-related cytotoxicity could be removed by adsorption with melanoma cells. The cells used in adsorptions acquired a granular coat of Ig by immunofluorescence test. BIBLIOGRAPHIC REFERENCE: Twomey, J.J., Rossen, R.D., Lewis, V.M., Laughter, A.H. and Douglass, C.C., Rheumatoid factor and tumor-host interaction, Proc. Nat. Acad. Sci. USA 73:2106-2108, 1976.